tbuckley/cabot-search huggingface dataset:
Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx
Authors: Shipra Gandhi, Mateusz Opyrchal, Melissa J Grimm, Ronald T Slomba, Kathleen M Kokolus, Agnieszka Witkiewicz, Kristopher Attwood, Adrienne Groman, Lauren Williams, Mary Lynne Tarquini, Paul K Wallace, Kah Teong Soh, Hans Minderman, Orla Maguire, Tracey L O’Connor, Amy P Early, Ellis G Levine, Pawel Kalinski
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical studies, suggested that their systemic application can reprogram local TMEs. Methods Six evaluable patients (33–69 years) with metastatic triple-negative breast cancer received six doses of systemic chemokine-modulating (CKM) regimen composed of TLR3 ligand (rintatolimod; 200 mg; intravenous), IFN-α2b (20 MU/m 2 ; intravenous) and COX2 inhibitor (celecoxib; 2×200 mg; oral) over 2 weeks. The predetermined primary endpoint was the intratumoral change in the expression of CTL marker, CD8α, in the post-CKM versus pre-CKM tumor biopsies. Patients received follow-up pembrolizumab (200 mg, intravenously, every 3 weeks), starting 3–8 days after completion of CKM. Results Post-CKM biopsies showed selectively increased CTL markers CD8α (average 10.2-fold, median 5.5-fold, p=0.034) and granzyme B (GZMB; 6.1-fold, median 5.8-fold, p=0.02), but not FOXP3 (Treg marker) relative to HPRT1 expression, resulting in the increases in average CD8α/FOXP3 ratio and GZMB/FOXP3 ratio. CKM increased intratumoral CTL-attractants CCL5 and CXCL10, but not Treg-attractants CCL22 or CXCL12. In contrast, CD8 + T cells and their CXCR3 + subset showed transient decreases in blood. One clinical response (breast tumor autoamputation) and three stable diseases were observed. The patient with clinical response remains disease free, with a follow-up of 46 months as of data cut-off. Conclusions Short-term systemic CKM selectively increases CTL numbers and CTL/Treg ratios in the TME, while transiently decreasing CTL numbers in the blood. Transient effects of CKM suggest that its simultaneous application with checkpoint blockade and other forms of immunotherapy may be needed for optimal outcomes.
The interplay of drug therapeutics and immune responses to SARS-CoV-2
Authors: Valeria Fumagalli, Matteo Iannacone
Journal: Cellular and Molecular Immunology (2023)

Abstract The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative responses. While vaccines form the frontline of defense, antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures, particularly for those unable or unwilling to be vaccinated. This review delves into the potential influence of nirmatrelvir on enduring immunity. In parallel, the potential of drug repurposing is explored, with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory properties. The importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.
Intranasal G5‐BGG/pDNA Vaccine Elicits Protective Systemic and Mucosal Immunity against SARS‐CoV‐2 by Transfecting Mucosal Dendritic Cells
Authors: Han Zhang, Zezhong Liu, Hongye Lihe, Linwei Lu, Zongxu Zhang, Shengmin Yang, Nana Meng, Yin Xiong, Xingyan Fan, Zhikai Chen, Weiyue Lu, Cao Xie, Min Liu
Journal: Advanced Healthcare Materials (2023)

Abstract Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal‐associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5‐BGG and antigen‐expressing plasmid DNA (pSP), named G5‐BGG/pSP complex, is developed to activate NALT and to promote both systemic and mucosal immune defense. G5‐BGG/pSP could traverse mucosal barriers and deliver DNA to the target cells because of its superior nasal retention and permeability characteristics. The intranasal G5‐BGG/pSP complex elicits robust antigen‐specific immune responses, such as the notable production of IgG antibody against several virus variants. More importantly, it induces elevated levels of antigen‐specific IgA antibody and a significant expansion of the lung‐resident T lymphocyte population. Notably, the intranasal G5‐BGG/pSP complex results in antigen expression and maturation of dendritic cells in nasal mucosae. These findings exhibit the potential of G5‐BGG, a novel cationic material, as an effective gene carrier for intranasal vaccines to obtain robust systemic and mucosal immunity.
Cooperative Response to Endocardial Notch Reveals Interaction With Hippo Pathway
Authors: Luis Luna-Zurita, Brenda Giselle Flores-Garza, Dimitrios Grivas, Marcos Siguero-Álvarez, José Luis de la Pompa
Journal: Circulation Research (2023)

The endocardium is a crucial signaling center for cardiac valve development and maturation. Genetic analysis has identified several human endocardial genes whose inactivation leads to bicuspid aortic valve formation and calcific aortic valve disease, but knowledge is very limited about the role played in valve development and disease by noncoding endocardial regulatory regions and upstream factors.
Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM
Authors: Sharon Cresci, Richard G. Bach, Sara Saberi, Anjali T. Owens, John A. Spertus, Sheila M. Hegde, Neal K. Lakdawala, Ester Kim Nilles, Daniel M. Wojdyla, Amy J. Sehnert, Andrew Wang
Journal: Circulation (2023)

Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy).
Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function
Authors: Weiyi Xu, Cyrielle Billon, Hui Li, Andrea Wilderman, Lei Qi, Andrea Graves, Jernie Rae Dela Cruz Rideb, Yuanbiao Zhao, Matthew Hayes, Keyang Yu, McKenna Losby, Carissa S. Hampton, Christiana M. Adeyemi, Seok Jae Hong, Eleni Nasiotis, Chen Fu, Tae Gyu Oh, Weiwei Fan, Michael Downes, Ryan D. Welch, Ronald M. Evans, Aleksandar Milosavljevic, John K. Walker, Brian C. Jensen, Liming Pei, Thomas Burris, Lilei Zhang
Journal: Circulation (2023)

Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.
Nitric Oxide Modulates Ca <sup>2+</sup> Leak and Arrhythmias via S-Nitrosylation of CaMKII
Authors: Amelia S. Power, Esther U. Asamudo, Luke P.I. Worthington, Chidera C. Alim, Raquel E. Parackal, Rachel S. Wallace, Obialunanma V. Ebenebe, Joan Heller Brown, Mark J. Kohr, Donald M. Bers, Jeffrey R. Erickson
Journal: Circulation Research (2023)

Nitric oxide (NO) has been identified as a signaling molecule generated during β-adrenergic receptor stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca
Distinguishing involuntary autobiographical memories and déjà vu experiences: Different types of cues and memory representations?
Authors: Lia Kvavilashvili, Ioanna Markostamou
Journal: Behavioral and Brain Sciences (2023)

Abstract Although involuntary autobiographical memories (IAMs) and déjà vu have important shared characteristics, in this commentary, we focus on potential differences that may question the argument that two phenomena lie on a continuum. We propose that differences in their frequency and autonoetic consciousness could be explained by different types of cues and memory representations involved in experiencing IAMs and déjà vu.
The Emerging Spectrum of Somatic Mutation in Rheumatic Disease: Clonal Hematopoiesis Connects Aging With Giant Cell Arteritis
Authors: Richard Bucala, Betty P. Tsao
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Déjà vu and involuntary autobiographical memories as two distinct cases of familiarity in patients with Alzheimer's disease
Authors: Joanna Gautier, Samuel Bulteau, Guillaume Chapelet, Mohamad El Haj
Journal: Behavioral and Brain Sciences (2023)

Abstract The continuum between involuntary autobiographical memories and déjà vu, as proposed by Barzykowski and Moulin, can be better defined by considering research on autobiographical retrieval in patients with Alzheimer's disease. Although autobiographical retrieval in patients with Alzheimer's disease can generally be associated with a sense of familiarity, involuntary retrieval can trigger an autonoetic experience of retrieval in these patients.
What do we gain (or lose) by considering déjà vu a part of autobiographical memory?
Authors: Søren Risløv Staugaard
Journal: Behavioral and Brain Sciences (2023)

Abstract I argue the relationship between déjà vu and autobiographical memory is not continuous, but more akin to a path diagram. The starting points might be overlapping, but eventually the paths diverge dependent on whether there is memory content to be retrieved. I am worried that considering déjà vu as part of autobiographical memory solves more problems than it creates.
Involuntary memories are not déjà vu
Authors: Sami Gülgöz, Irem Ergen
Journal: Behavioral and Brain Sciences (2023)

Abstract The proposed framework can benefit from integrating predictive processing into the explanation of déjà vu which corresponds to interrupted prediction. Déjà vu is also accompanied by familiarity. However, considerable ambiguity is inherent in familiarity, which necessitates elaboration of this construct. Research findings on involuntary autobiographical memories and déjà vu show discrepancies, and clustering these constructs can be counterproductive for research.
Involuntary autobiographical memories and déjà vu: When and why attention makes a difference
Authors: Manila Vannucci, Maciej Hanczakowski
Journal: Behavioral and Brain Sciences (2023)

The target article claims that involuntary autobiographical memories and déjà vu are based on the same retrieval processes, although they result in different phenomenological states. Here we argue that the differential engagement of attention at various stages of memory may be one of the determinants of when common retrieval processes give rise to such different experiences.
The need for a unified framework: How Tulving's framework of memory systems, memory processes, and the SPI-model can guide and sharpen the understanding of déjà vu and involuntary autobiographical memories and add to conceptual clarity
Authors: Hans J Markowitsch, Andreas Kordon, Angelica Staniloiu
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin link déjà vu and involuntary autobiographical memories to the process of retrieval. They make no reference to Tulving's SPI-model. In this, it is proposed that information is acquired serially (S), stored in parallel (P), and retrieved independently (I). This model offers an alternative, elegant, view of involuntary autobiographical memory retrieval, as well as of déjà vus.
Involuntary memory signals in the medial temporal lobe
Authors: Haopei Yang, Chris B. Martin, Stefan Köhler
Journal: Behavioral and Brain Sciences (2023)

Abstract We highlight recent progress in neuroimaging and neuropsychological research on memory mechanisms in the medial temporal lobe that speaks to the involuntary nature of memory retrieval processes. We suggest that evidence form these studies supports Barzykowski and Moulin's proposal that memory signals involved in experiences of familiarity and déjà vu can be generated in the absence of retrieval intentionality.
Further advancing theories of retrieval of the personal past
Authors: Krystian Barzykowski, Chris J A Moulin
Journal: Behavioral and Brain Sciences (2023)

Abstract In our target article, we presented the idea that involuntary autobiographical memories (IAMs) and déjà vu may both be based on the same retrieval processes. Our core claim was thus straightforward: Both can be described as “involuntary” or spontaneous cognitions, where IAMs deliver content and déjà vu delivers only the feeling of retrieval. Our proposal resulted in 27 commentaries covering a broad range of perspectives and approaches. The majority of them have not only amplified our key arguments but also pushed our ideas further by offering extensions, refinements, discussing possible implications and providing additional empirical, neuroscientific and clinical support. The discussion launched by the commentaries proves to us the importance of bringing IAMs and déjà vu into mainstream discussions of memory retrieval processes.
On the frequency and nature of the cues that elicit déjà vu and involuntary autobiographical memories
Authors: Ricardo Morales-Torres, Felipe De Brigard
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin suggest that déjà vu and involuntary autobiographical memories recruit similar retrieval processes. Here, we invite the authors to clarify three issues: (1) What mechanism prevents déjà vu to happen more frequently? (2) What is the role of semantic cues in involuntary autobiographical retrieval? and (3) How déjà vu relates to non-believed memories?
Déjà vu: A botched memory operation, illegitimate to start with
Authors: Debora Stendardi, Anindita Basu, Alessandro Treves, Elisa Ciaramelli
Journal: Behavioral and Brain Sciences (2023)

Abstract Rather than a natural product, a computational analysis leads us to characterize déjà vu as a failure of memory retrieval, linked to the activation in neocortex of familiar items from a compositional memory in the absence of hippocampal input, and to a misappropriation by the self of what is of others.
Oh it's me again: Déjà vu, the brain, and self-awareness
Authors: Samantha Zorns, Claudia Sierzputowski, Matthew Pardillo, Julian Paul Keenan
Journal: Behavioral and Brain Sciences (2023)

Abstract Déjà vu and involuntary autobiographical memories (IAMs) are differentiated by a number of factors including metacognition. In contrast to IAMs, déjà vu activates regions associated with self-awareness including the right dorsolateral prefrontal cortex.
Evolutionary mismatch and anomalies in the memory system
Authors: Walter Veit, Heather Browning
Journal: Behavioral and Brain Sciences (2023)

Abstract In order to understand involuntary autobiographical memories and déjà vu experiences, we argue that it is important to take an evolutionary medicine perspective. Here, we propose that these memory anomalies can be understood as the outcomes of an inevitable design trade-off between type I and type II errors in memory processing.
The misidentification syndromes and source memory deficits with their neuroanatomical correlates from neuropsychological perspective
Authors: Rafał Sikorski, Emilia J. Sitek
Journal: Behavioral and Brain Sciences (2023)

Abstract The suggested model is discussed with reference to two clinical populations with memory disorders – patients with misidentification syndromes and those with source memory impairment, both of whom may present with (broadly conceived) déjà vu phenomenon, without insight into false feeling of familiarity. The role of the anterior thalamic nucleus and retrosplenial cortex for autobiographical memory and familiarity is highlighted.
On pattern completion, cues and future-oriented cognition
Authors: Donna Rose Addis, Karl K Szpunar
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin's view on involuntary autobiographical memory focuses on automatic activation of representations and inhibitory control mechanisms. We discuss how and when a known neural mechanism – pattern completion – may result in involuntary autobiographical memories, the types of cues that may elicit this phenomenon and consider interactions with future-oriented cognition.
Intracranial electrical brain stimulation as an approach to studying the (dis)continuum of memory experiential phenomena
Authors: Jonathan Curot, Anaïs Servais, Emmanuel J. Barbeau
Journal: Behavioral and Brain Sciences (2023)

Abstract Déjà vu and involuntary autobiographical memories (IAM) can be induced by intracranial electric brain stimulation in epileptic patients, sometimes in the same individual. We suggest that there may be different types of IAM which should be taken into account and provide several ideas to test the hypothesis of a continuity between IAM and déjà vu phenomena.
The relation of subjective experience to cognitive processing
Authors: Bennett L. Schwartz, Ali Pournaghdali
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin argue that common memory processes form the basis of involuntary autobiographical memory and the déjà vu experience. We think that they underemphasize the potential dissociability between processes that enact retrieval and the processes that produce conscious experience. We propose that retrieval and conscious experience result from different processes in both involuntary autobiographical memory and déjà vu experiences.
Does inhibitory (dys)function account for involuntary autobiographical memory and déjà vu experience?
Authors: Thomas F. Burns
Journal: Behavioral and Brain Sciences (2023)

Abstract External cues and internal configuration states are the likely instigators of involuntary autobiographical memories (IAMs) and déjà vu experience. Indeed, Barzykowski and Moulin discuss relevant neuroscientific evidence in this direction. A complementary line of enquiry and evidence is the study of inhibition and its role in memory retrieval, and particularly how its (dys)function may contribute to IAMs and déjà vu.
A spontaneous neural replay account for involuntary autobiographical memories and déjà vu experiences
Authors: Mohith M. Varma, Rongjun Yu
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin argue both involuntary autobiographical memories and déjà vu experiences rely on the same involuntary memory retrieval processes but their underlying neurological basis remains unclear. We propose spontaneous neural replay in the default mode network (DMN) and hippocampus as the basis for involuntary autobiographical memories, whereas for déjà vu experiences such transient activation is limited to the DMN.
Neuropsychological predictions on involuntary autobiographical memory and déjà vu
Authors: Christine Bastin
Journal: Behavioral and Brain Sciences (2023)

Abstract I strongly support Barzykowski and Moulin in their proposal that common retrieval mechanisms can lead to distinct phenomenological memory experiences. I emphasize the importance of one of these mechanisms, namely the attribution system. Neuropsychological studies should help clarifying the role of these retrieval mechanisms, notably in cases of medial temporal-lobe lesions and cases of dementia.
Are involuntary autobiographical memory and déjà vu cognitive failures?
Authors: John H. Mace
Journal: Behavioral and Brain Sciences (2023)

Abstract This commentary supports Barzykowski and Moulin's model, but departs from it on the question of functionality, where IAMs and déjà vu fractionate. The authors seem to say that IAMs are functional, while déjà vu is not. As there is no hard evidence supporting the idea that IAMs are functional, I argue that both phenomena should be viewed as cognitive failures.
A rational analysis and computational modeling perspective on IAM and déjà vu
Authors: Justin Li, Steven Jones, John Laird
Journal: Behavioral and Brain Sciences (2023)

Abstract The proposed memory architecture by Barzykowski and Moulin is compelling, and could be improved by incorporating a rational analysis of the functional roles of involuntary autobiographical memory and déjà vu. Additionally, modeling these phenomena computationally would remove ambiguities from the proposal. We provide examples of past work that illustrate how the phenomena may be described more precisely.
Accommodating the continuum hypothesis with the déjà vu/déjà vécu distinction
Authors: Denis Perrin
Journal: Behavioral and Brain Sciences (2023)

Abstract On Barzykowski and Moulin's continuum hypothesis, déjà vu and involuntary autobiographical memories (IAMs) share their underpinning neurocognitive processes. A discontinuity issue for them is that familiarity and episodic recollection exhibit different neurocognitive signatures. This issue can be overcome, I say, provided the authors are ready to distinguish a déjà vécu/episodic IAM continuity and a déjà vu/semantic IAM continuity.
From jamais to déjà vu: The respective roles of semantic and episodic memory in novelty monitoring and involuntary memory retrieval
Authors: Louis Renoult, J. Bruno Debruille
Journal: Behavioral and Brain Sciences (2023)

Abstract Barzykowski and Moulin's model proposes that déjà vu and involuntary autobiographical memories are the result of a continuously active memory system that tracks the novelty of situations. Déjà vu would only have episodic content and concern interpretation of prior experiences. We argue that these aspects of the model would gain to be clarified and explored further and we suggest possible directions.
A possible shared underlying mechanism among involuntary autobiographical memory and déjà vu
Authors: Anne M. Cleary, Cati Poulos, Caitlin Mills
Journal: Behavioral and Brain Sciences (2023)

Abstract We propose that IAM and déjà vu may not share a placement on the same gradient, per se, but the mechanism of cue familiarity detection , and a major differentiating factor between the two metacognitive experiences is whether the resulting inward directed search of memory yields retrieved content or not. Déjà vu may manifest when contentless familiarity detection is inexplicable by the experiencer.
Correction: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: a Phase I Dose Escalation and Expansion Study
Authors: Andrea Wang-Gillam, Kian-Huat Lim, Robert McWilliams, Rama Suresh, Albert C. Lockhart, Amberly Brown, Marcus Breden, Jad I. Belle, John Herndon, Savannah J. Bogner, Katrina Pedersen, Benjamin Tan, Nicholas Boice, Abhi Acharya, Mina Abdiannia, Feng Gao, Harry H. Yoon, Mojun Zhu, Nikolaos A. Trikalinos, Lee Ratner, Olivia Aranha, William G. Hawkins, Brett H. Herzog, David G. DeNardo
Journal: Clinical Cancer Research (2023)

In the original version of this article (1), the Results section and the legend for Fig. 2 incorrectly stated that Patient 01–046’s heart failure was possibly related to the studied drugs (pembrolizumab, defactinib, and gemcitabine) when it was unrelated to the drugs; in addition, Table 2 incorrectly indicated that defactinib was possibly related to a different patient's heart failure. These errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret the errors.